Lynch syndrome identification in a Brazilian cohort of endometrial cancer screened by a universal approach.

Autor: Rosa RCA; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Regional Blood Center at University Hospital of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. Electronic address: reginaldoallves@usp.br., Santis JO; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Regional Blood Center at University Hospital of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. Electronic address: jolisantis@gmail.com., Teixeira LA; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. Electronic address: teixeiralorena.alves@gmail.com., Molfetta GA; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Regional Blood Center at University Hospital of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. Electronic address: gamolf@fmrp.usp.br., Dos Santos JTT; Post-graduate Program in Public Health Nursing, Ribeirão Preto College of Nursing, University of São Paulo, Ribeirão Preto, Brazil. Electronic address: thalitatargino@usp.br., Ribeiro VDS; Inter-institutional Doctoral Program in Nursing, Ribeirão Preto College of Nursing, University of São Paulo, Ribeirão Preto, Brazil. Electronic address: vasaribeiro@gmail.com., Chahud F; Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. Electronic address: fchahud@fmrp.usp.br., Ribeiro-Silva A; Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. Electronic address: arsilva@fmrp.usp.br., Brunaldi MO; Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. Electronic address: mabrunaldi@fmrp.usp.br., Silva WA Jr; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Regional Blood Center at University Hospital of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. Electronic address: wilsonjr@usp.br., Ferraz VEF; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Center for Medical Genomics at Clinical Hospital of the Ribeirão Preto Medical School, University of São Paulo, Brazil. Electronic address: vferraz@usp.br.
Jazyk: angličtina
Zdroj: Gynecologic oncology [Gynecol Oncol] 2020 Oct; Vol. 159 (1), pp. 229-238. Date of Electronic Publication: 2020 Jul 18.
DOI: 10.1016/j.ygyno.2020.07.013
Abstrakt: Objective: To report the frequency of Lynch syndrome (LS) in a cohort of patients from Southeast Brazil bearing endometrial cancer (EC), using a tumor screening universal approach.
Methods: A total of 242 endometrial carcinomas were screened by immunohistochemistry (IHC) and microsatellite instability (MSI) for detection of DNA mismatch repair deficiency (dMMR). MLH1 methylation was assessed to identify sporadic cases. Patients with dMMR tumors were recruited for germline variant analysis by next-generation sequencing of the MLH1, MSH2, MSH6, PMS2, and EPCAM genes.
Results: Ninety-three out of 242 tumors (38.5%) were classified as dMMR based on MSI and IHC results. Of these, 54 cases were selected for germline analysis, and 37/54 (68.5%) were available for sequencing. Ten patients (10/37, 27%) harbored germline pathogenic or likely pathogenic variants, most of them in the MSH6 gene (4/10, 40%). Seven variants of uncertain significance were found. Eight novel germline variants were identified. The LS prevalence in our cohort was of at least 4.1%. LS patients presented lower mean age at cancer diagnosis compared with patients diagnosed with sporadic EC. Individuals with dMMR tumors, without germline pathogenic variants detected in LS-genes ("Lynch-like" syndrome), had an intermediate mean age at cancer diagnosis between LS and sporadic cases.
Conclusion: This is the first report of the LS prevalence in EC screened by a universal approach in Brazil. Our findings contribute to a better understanding of the mutational landscape of this syndrome in Brazil, which is relevant for improved identification, genetic counseling, prevention and control of cancer in LS.
Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest regarding the research, authorship, and/or publication of this article.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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